Lapatinib and Doxorubicin Hydrochloride Liposome in Treating Patients With Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00316875
Recruitment Status : Completed
First Posted : April 21, 2006
Last Update Posted : November 8, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
William Gradishar, Northwestern University

April 19, 2006
April 21, 2006
November 8, 2013
May 2006
August 2011   (Final data collection date for primary outcome measure)
  • Cardiac safety [ Time Frame: Throughout treatment and up to 30 days post-treatment ]
  • Maximum tolerated dose [ Time Frame: After the first cycle of therapy ]
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Complete list of historical versions of study NCT00316875 on Archive Site
  • Pharmacokinetic profiles [ Time Frame: After treatment completion for 12 patients treated at the maximum tolerated dose ]
  • Efficacy [ Time Frame: At time of disease progression ]
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Lapatinib and Doxorubicin Hydrochloride Liposome in Treating Patients With Metastatic Breast Cancer
A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of Lapatinib in Combination With Liposomal Doxorubicin in Patients With Metastatic Breast Cancer

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with doxorubicin hydrochloride liposome may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of doxorubicin hydrochloride liposome when given together with lapatinib in treating patients with metastatic breast cancer.



  • Evaluate the safety, tolerability, and feasibility of pegylated doxorubicin HCl liposome (PLD) when administered with lapatinib, particularly in terms of cardiac safety, in patients with metastatic breast cancer.
  • Determine the optimally tolerated regimen (OTR) of PLD when administered with lapatinib in these patients.


  • Determine the pharmacokinetic profiles of lapatinib and PLD when given in combination at the OTR.
  • Describe any preliminary evidence of efficacy of lapatinib and PLD in these patients.

OUTLINE: This is an open-label, dose-escalation study of pegylated doxorubicin HCl liposome (PLD).

Patients receive oral lapatinib once daily on days 1-28 and PLD IV over at least 30 minutes on day 1. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Lapatinib may be continued alone in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PLD until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.

After completing study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Breast Cancer
  • Drug: lapatinib ditosylate
    1500 mg orally daily for as long as patients remain on trial (up to 8 cycles).
  • Drug: Doxil
    Administered intravenously (IV) every 4 weeks in a dose-escalating fashion according to a set schedule
    Other Names:
    • Doxorubicin HCL Liposome Injection
    • Dox-SL
Experimental: Lapatinib Ditosylate and Doxil
  • Drug: lapatinib ditosylate
  • Drug: Doxil
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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August 2011
August 2011   (Final data collection date for primary outcome measure)


  • Histologically confirmed adenocarcinoma of the breast with evidence of metastatic disease

    • Epidermal growth factor receptor (EGFR) and/or erbB2 positivity not required
  • Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques OR as ≥ 10 mm by spiral CT scan
  • No known brain metastases or leptomeningeal disease
  • Hormone receptor status not specified


  • Male or female patients
  • Menopausal status not specified
  • Life expectancy ≥ 12 weeks
  • ECOG performance status 0-1
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • LVEF ≥ 50%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow and retain oral medication
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
  • No gastrointestinal (GI) tract disease resulting in inability to take oral medication
  • No malabsorption syndrome or requirement for IV alimentation
  • No uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)


  • Prior trastuzumab (Herceptin ®) allowed
  • Prior anthracyclines allowed provided total dose of doxorubicin hydrochloride ≤ 240 mg/m² or epirubicin ≤ 600 mg/m²
  • More than 4 weeks since prior major surgery, hormonal therapy (other than replacement therapy), chemotherapy (6 weeks for nitrosoureas or mitomycin C), or radiotherapy and recovered
  • No prior surgical procedures affecting absorption
  • No prior EGFR-targeting therapies
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors
  • At least 7 days since prior and no concurrent gastric pH modifiers

    • Antacids allowed within 1 hour before and after lapatinib dosing
  • At least 14 days since prior and no concurrent CYP3A4 inducers, including dexamethasone or dexamethasone equivalent dose > 1.5 mg/day
  • At least 6 months since prior and no concurrent amiodarone
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent prophylactic growth factor support
  • No concurrent herbal medications
  • No other concurrent investigational agents or anticancer therapy
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
NU 05B5
P30CA060553 ( U.S. NIH Grant/Contract )
NCI-2011-00325 ( Other Identifier: NCI CTRP# )
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William Gradishar, Northwestern University
Northwestern University
National Cancer Institute (NCI)
Principal Investigator: William J Gradishar, M.D. Robert H. Lurie Cancer Center
Northwestern University
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP